Stimulation mediated sensory enhancement of the urethral afferents

描述（由申请人提供）：尿潴留是一种泌尿道疾病，使成千上万的人无法正确排空膀胱内的内容物。尿潴留可能由许多原因引起，如自然衰老、急性创伤（特别是在手术过程中）、糖尿病、多发性硬化症等。尽管原因多种多样，但大多数尿潴留的一个共同特征是检测尿道液体流动的神经敏感性降低。这种敏感性的降低反过来又限制了自然控制膀胱排尿的反射效果。我们假设，增强尿道的敏感性将减轻许多与潴留相关的症状，使反射再次正常运作。本提案的工作将证明提高尿道敏感性是可能的。为了实现这种增强，我们将使用一种称为随机共振的过程，在这种过程中，我们将亚阈值水平的电噪声（数量小到不能被感觉神经元检测到）直接注入尿道。这将在大鼠尿路模型中进行。随机共振已经在其他生物感觉系统中取得了成功，我们假设这些不可检测的扰动将降低尿道感觉神经元的激活阈值，有效地增加它们对血流的敏感性。我们将通过记录阴部神经来证明我们的发现，阴部神经将感觉信息从尿道传递到脊髓。我们将比较在一定的流量范围内，在有刺激和没有刺激的情况下，阴部神经对尿道液体流动的反应。我们可以得出结论，如果在有刺激的情况下观察到的神经活动比没有刺激的情况下更多，那么灵敏度就会增强，如果在有刺激的情况下可以检测到较慢的流量，这也将作为灵敏度增强的证据。最后，结合动物实验建立下尿路随机共振的数学模型。这个模型将允许我们模拟许多不同类型的刺激和流量，以更好地指导动物工作。使用该模型，我们可以研究范围广泛的实验参数，比我们使用生物系统测试的参数要多得多。我们将使用最佳刺激参数和流量的模型估计，为我们自己提供最佳的成功机会，以提高尿道敏感性。

DESCRIPTION (provided by applicant): Urinary retention is a disease of the urinary tract that prevents hundreds of thousands of people from properly emptying the contents of their bladder. Urinary retention can be caused by many things such as natural aging, acute trauma (especially during surgical procedures), diabetes, multiple sclerosis and others. Despite the range of causes, a feature common to most cases of urinary retention is a reduced neural sensitivity for detecting fluid flow in the urethra. This reduction in sensitivity, in turn, limits the effectivenes of reflexes that naturally control bladder voiding. We hypothesize that enhancing urethral sensitivity will mitigate many of the symptoms associated with retention by allowing the reflexes to once again function properly. The work in this proposal will demonstrate that it is possible to enhance urethral sensitivity. To accomplish this enhancement we will use a process called stochastic resonance, where we inject sub-threshold levels of electrical noise (amounts small enough that they cannot be detected by the sensory neurons) directly into the urethra. This will be done in a rat model of the urinary tract. Stochastic resonance has been successful in other biological sensory systems and we hypothesize that these undetectable perturbations will lower the activation threshold of the urethral sensory neurons, effectively increasing their sensitivity o flow. We will demonstrate our findings by recording from the pudendal nerve, which carries sensory information from the urethra to the spinal cord. We will compare the pudendal nerve's response to fluid flow in the urethra both with and without the stimulation at a range of flowrates We can conclude that sensitivity was enhanced if more neural activity is observed in the presence of the stimulation than without it, and if slower flowrates can be detected with the stimulation it will also serve as evidence of enhanced sensitivity. Finally, a mathematical model of stochastic resonance in the lower urinary tract will be developed in tandem with the animal experiments. This model will allow us to simulate many different types of stimulation and flowrates to better guide the animal work. Using the model we can investigate a wide range of experiment parameters, many more than we could test using the biological system. We will use the model estimates of the optimal stimulation parameters and flowrates to give ourselves the best chance of success for enhancing urethral sensitivity.